摘要:

Dextran in lactated Ringer's solution (20 ml/ kg) was infused for 1 hour into anesthetized dogs with slnoaortic denervation and vagotomy (deafferentatlon; n=10) and dogs treated with hexamethonium (de-efferentation; n = 13) to compare with our previous observation in dogs with an intact autonomic nervous system (control, n-34). During the infusion, increase in blood pressure associated with increase in cardiac output was observed in all three groups. The increases in blood pressure were larger in the two groups with an impaired autonomic nervous system. In the recovery period, the control dogs and the hexamethonium-treated dogs showed gradual increases in total peripheral resistance and in vasoconstricted hypertension 3 hours after stopping the infusion. In contrast, the dogs with sinoaortic denervation and vagotomy did not show any increase in total peripheral resistance. The vasoconstricted groups showed peaks of natriuresis soon after the infusion, not 3 hours after the infusion when vasoconstriction was observed, although the dogs with deafferentation did not show a significant increase in natriuresis. Norepinephrine (0.5 μg/kg) was administered intravenously before and after volume expansion, and the pressor responses in the three groups after volume expansion were enhanced similarly (143%, 128%, and 136%, respectively). These results indicate that the afferent signals from peripheral vessels to the brain contribute to the production of vasoconstricted hypertension after acute volume expansion and that the vasoconstriction is independent of pressor hypersensitivity and is dissociated in time from the natriuresis.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal mkrovascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computerassisted videomicroscopy daring alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half-maximal inhibitory concentration (IC50) (WKY, 63 ± 27 vs. SHR, 60 ± 32 nM). The pressure-activation curves for ILAs in SHR and WKY were similar. In contrast, the pressure-activation curve for afferent arterioles in SHR kidneys exhibited a rightward shift, which was observed at every segment of the afferent arteriole (i.e., near ILA, at midportion, and near glomerulus). These findings demonstrate that the HA and the afferent arteriole both possess the ability to constrict in response to increased pressure, whereas this property is lacking in the efferent arteriole. Hypertension was associated with a compensatory shift in the pressure response of the afferent arteriole, such that higher RAPs were required to elicit vasoconstriction in this vessel.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Antiarrhythmic drug effects on maximal upstroke velocity (Vmax) are frequency dependent, which implies that the effects of these drugs on conduction should also be rate dependent. Previous in vivo studies have been limited by assumptions about unchanging propagation pathway, and by the empirical use of a first-order recovery model. To explore time-dependent antiarrhythmic drug-induced conduction slowing in vivo, we used 56-electrode epicardial mapping in chloralose-anesthetized dogs with formalin-induced atrioventricular block. Intervaldependent changes in conduction time were assessed under control conditions and then after three loading and maintenance infusions of procainamide. Under control conditions, epicardial activation time (86 ± 26 msec at a basic cycle length of 300 msec) was unchanged (87 ± 24 msec) by pauses up to 6.6 ± 2.2 seconds. Procainamide caused conduction slowing that dissipated as a function of recovery interval, with 94 ± 6% recovery over a maximum pause of 6.7 ± 1.5 seconds, but did not alter activation pattern. Drug-induced changes in conduction were evaluated by use of a mathematical model assuming phase 0 inward current proportional to conduction velocity squared. Conduction changes were better fitted by this "quadratic model" (least sum of squared deviations 3.9 ×l0−3by mapping in five dogs, 2.7 ×l0−3by use of QRS duration in nine dogs) than by a monoexponential model (sum of squared deviations 5.7×l0−3by mapping, 3.4×l0−2with QRS;<0.01 vs. quadratic model for each). As predicted by theoretical analysis, recovery time constants from the quadratic model were similar to time constants for procainamideinduced changes in VmaxIn vitro, and significantly longer than values obtained with a monoexponential model. Drug-induced changes in QRS duration were highly correlated with simultaneous changes measured by epicardial mapping (r=0.95, p<0.001), indicating that QRS duration is a valid index of drug effects on ventricular conduction. We concluded that procainamide causes interval-dependent changes in ventricular conduction in vivo that are consistent with a proportional relation between phase 0 inward current and the square of conduction velocity. These observations have important potential implications for the dosedependent and heart rate-dependent effects of antiarrhythmic drugs.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To determine whether the variation in the magnitude of work load sustained by the left and right ventricles during adulthood and senescence affects the load-dependent aspect of relaxation, posterior papillary muscles from the left and right ventricles of rats at 4, 10, and 20 months of age were studied under variably loaded conditions in vitro. Because of differences between the life spans of Fischer and Sprague-Dawicy rats, the functional characteristics of relaxation were investigated to evaluate the possibility of a differential age-associated response in these two strains of animals. The kinetic performance of the diastolic phase of myocardial contraction was measured by assessing the relative time during which load bearing occurred in a series of afterloaded isotonic twitches. This measurement was expressed as the ratio of the duration of afteiioaded isotonic shortening and relengthening to the time required for isometric force to decline to the same level daring isometric relaxation. A ratio of less than unity identified a load-dependent state whereas a value greater than one reflected a load-independent condition. Results snowed that the right myocardium was completely load independent whereas the left myocardium was fully load dependent at all physiological afterloads. Aging reduced the load independence of the right ventricle and the load dependence of the left ventricle in Fischer rats. In contrast, no aging effect on the properties of afteiioaded isotonic relaxation was seen in Sprague-Dawiey rats. In conclusion, distinct differences exist in the mechanical dynamics of inactivation between the left and right ventricular myocardium. Aging reduced these variations in Fischer rats but had no apparent influence in Sprague-Dawiey animals up to 20 months after birth.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2=42 ± l mm Hg) in the presence of indomethacin (2.8 ×K−5M). This moderate degree of hypoxia inhibited (p<0.05) endothelium-dependent but not endotheliumindependent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p<0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than hi endotheliumdenuded vessels (0.70 ± 0.12 vs. 0.09 ± 0.03 g, respectively;p<0.01). This increase in tension was reduced in the presence of hemoglobin (l×l0−6M; p<0.01), methylene blue (l × l×−7M; p<0.01), and hydroqulnone (l×l0−6M;<0.01) in endothelium-intact but not in endotheliumdenuded rings. Hypoxia also reduced basal cyclic GMP content in endothelium-intact phenylephrine-precontracted rings (1.23 ± 0.22 vs. 0.79 ± 0.19 pmol/mg protein;p<0.05). These data suggest that the transient vasoconstriction induced by hypoxia in these large pulmonary arteries is due partially to the inhibition of basal EDRF production. The observed pharmacological responses imply that the site of hypoxia-induced inhibition of endothelium-dependent dilation is distal to receptor-mediated events in the endothelial cell and proximal to activation of guanylate cyclase In the vascular smooth muscle.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Adenosine, an intermediate product in the metabolism of ATP, is thought to produce vasodilatation in all vascular beds with the exception of the kidney. Due to its theoretical potential as a pulmonary vasodilator, we studied the hemodynamic effects of adenosine in the pulmonary vasculature of chronically instrumented awake sheep. Adenosine produced significant pulmonary vasoconstriction instead of the expected vasodilatation. Bolus injections of adenosine into the superior vena cava produced a dose-dependent increase in pulmonary artery pressure that was entirely due to an increase in vascular resistance, since cardiac output decreased slightly. This effect is produced via activation of specific cell surface adenosine receptors, since it was blocked by the adenosine-receptor antagonists theophylline and dipropylsulfophenylxanthine. The cell type involved in adenosine-induced pulmonary vasoconstriction appears to be located within the lung, since vasoconstriction was blunted when adenosine was infused into the left atrium, distal to the lung. However, adenosine does not directly vasoconstrict the pulmonary vasculature, because its effect could be completely abolished by cyclooxygenase inhibition with either indomethacin or ibuprofen and by a thromboxane A2/prostaglandin endoperoxide-receptor antagonist (SQ 29,548). Adenosineinduced vasoconstriction was also greatly reduced after inhibition of thromboxane synthesis. Thus, adenosine produced pulmonary vasoconstriction through generation of a thromboxane/ endoperoxide product. Whether endogenous adenosine is involved in the generation of pulmonary vasoconstriction seen in pathophysiological states remains to be determined. To our knowledge, this is the first clear evidence for adenosine-induced vasoconstriction outside the kidney and for an interaction between adenosine and eicosanoid mechanisms.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The purpose of this study was to determine if arterial baroreflex control of sympathetic nerve traffic is impaired in heart failure. We recorded renal nerve activity during changes in arterial pressure while simultaneously recording from aortic baroreceptor afferent fibers in 10 dogs with heart failure induced by rapid ventricular pacing and in 10 sham animals. Sensitivity of the aortic baroreceptors (percent change in nerve activity per millimeters mercury change in mean arterial pressure) was reduced in the heart failure group (heart failure, 2.3 ± 0.3; sham, 3.6 ± 0.4, p=0.02). Despite the reduced sensitivity of aortic baroreceptors in heart failure, there was no difference in the baroreflex gain of renal nerve activity (heart failure, −5.5 ± 1.4; sham, −5.8 ± 1.3, p=NS). These values tended to decrease in both groups after vagotomy. The relation between baroreceptor input and renal sympathetic output, or central baroreflex gain (percent change in renal nerve activity divided by percent change in aortic nerve activity) was similar in both groups before vagotomy (heart failure, - 2.4 ± 0.6; sham, −2.3 ± 0.5, p=NS). Vagotomy reduced central gain in the sham group (−0.9 ± 0.1, p=0.03) but not in the heart failure group (−1.7 ± 0.5,/7=NS), suggesting that the contribution of vagal afferents in the baroreflex arc is reduced in heart failure. Baroreflex control of R-R interval was attenuated in heart failure when assessed by blood pressure elevation but not reduction, indicating abnormal parasympathetic but preserved cardiac sympathetic mechanisms in heart failure. Thus, dogs with heart failure exhibit reduced sensitivity of aortic baroreceptors but preserved baroreflex control of renal nerve activity. Reduced baroreceptor sensitivity with preservation of baroreflex control of sympathetic nerve activity may contribute to the sympathoexcitatory state known to exist in heart failure.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Neuropeptide Y (NPY) attenuates vagal effects on cardiac cycle length, presumably by inhibiting the release of acetylcholine from vagal nerve endings. We sought to determine if NPY inhibited the vagal effects on atrioventricular (AV) interval and atrial contraction in a manner similar to its inhibition of the vagal effects on cycle length. In 19 anesthetized dogs we measured the vagal effects on cycle length, AV Interval, and atrial contraction before and after 3-minute trains of sympathetic stimulation or before and after exogenous NPY (20 μg/kg i.v.). Three minutes after 10-Hz sympathetic stimulation, the vagal effects on cycle length and AV interval were attenuated by 52 ± 9% and 63 ± 8%, respectively. Phentolamine significantly augmented this attenuation, but propranolol had no appreciable effect. In the control group of animals or in the group that received phentolamine, the vagal effects on atrial contraction measured before and after sympathetic stimulation were not significantly different. In these two groups, however, the basal atrial contraction was reduced substantially after the cessation of sympathetic stimulation. Propranolol prevented this reduction in atrial contraction. After propranolol, the vagal effects on atrial contraction 3 minutes after sympathetic stimulation were attenuated by 31 ± 6%. Exogenous NPY had no direct effect on cycle length, AV interval, or atrial contraction, but exogenous NPY did persistently inhibit the vagal effects on each of these cardiac processes. Three minutes after NPY was given, the vagal effects on cycle length, AV interval, and atrial contraction were inhibited by 62 ± 7%, 69 ± 5%, and 68 ± 5%, respectively. We conclude that NPY attenuates the vagal effects on the atrial myocardium and on the sinus and AV nodes. In the absence of β-blockade, the inhibitory effect of neurally released NPY on the vagally induced decreases in atrial contraction may be masked by the reduction in the atrial contraction that occurs after sympathetic stimulation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, para sympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed by a variety of morphological and biochemical methods, but the functional status of innervation is not known. In the present study, we have used electrocardiography and field stimulation to determine the functional neural status of the three different innervation models. The RR and QTCcintervals were measured to assess the dominant autonomic tone and autonomic dysfunction in the heart. Even though the RR and QTCcintervals were found to be identical in sham and experimental embryos, field stimulation of superfused atria showed that the sympathetically aneural heart has functional cholinergic innervation but lacks any sympathetic response. Hearts from embryos which were parasympathetically ancural lacked a cholinergic response to field stimulation and were judged to be functionally parasympathetically aneural. Hearts with cholinergic ganglia reconstituted from the nodose placodes have normal RR and QTCcintervals as well as a normal cholinergic response to field stimulation. The results indicate that these neurons are functionally indistinguishable from neural crest-derived neurons.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To detect the functional significance of subendocardial hypoperfusion in the pressureoverloaded left ventricle, we studied subendocardial and subepicardial function and subendocardial and subepicardial blood flow simultaneously in seven dogs with left ventricular hypertrophy (left ventricle/body weight ratio, 7.2 g/kg) produced by chronic aortic banding. Seven normal dogs served as controls. Subendocardial and subepicardial segment lengths were measured by ultrasonic dimension gauges, and myocardial blood flow was measured with radioactive microspheres. Atrial pacing (180-200 beats/min for 5 minutes) was used to produce a chronotropic stress. In dogs with left ventricular hypertrophy, the subendocardial blood flow failed to increase during pacing compared with the baseline state (1.21 ± 0.17 vs. 1.22 ± 0.17 ml/min/g). Subendocardial shortening fraction deteriorated with pacing stress (before pacing, 30.6 ± 3.9%; after pacing, 24.2 ± 3.7%; <0.001). In controls, subendocardial blood flow increased from 1.32 ± 0.19 to 1.80 ± 0.19 ml/min/g during pacing, and shortening fraction was preserved (before pacing, 25.5 ± 3.9%; after pacing, 25.9 ± 3.3%). Subepicardial blood flow in dogs with hypertrophy increased from 1.54 ± 0.24 to 2.32 ± 0.34 ml/min/g, and subepicardial shortening fraction was maintained (before pacing, 10.4 ± 1.0%; after pacing, 10.5 ± 1.2%) as it was in controls (subepicardial blood flow, from 1.27 ± 0.18 to 2.12 ± 0.17 ml/min/g; shortening fraction, from 16.6 ± 2.5% to 15.5 ± 2.2%). We conclude that, with pacing stress in pressureoverload hypertrophy, subendocardial blood flow failed to increase. This abnormality corresponded with a deterioration in subendocardial contractile function.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID